Nejvíce citovaný článek - PubMed ID 16895955
Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance
The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.
- Klíčová slova
- cardiac surgery, coronary artery disease, diabetes mellitus, endoplasmic reticulum stress, epicardial fat, gene expression, inflammation, mitochondrial dysfunction,
- MeSH
- endoplazmatické retikulum genetika metabolismus MeSH
- exprese genu genetika MeSH
- kosterní svaly metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mitochondrie genetika metabolismus MeSH
- myokard metabolismus MeSH
- nemoci koronárních tepen genetika patofyziologie MeSH
- perikard metabolismus MeSH
- podkožní tuk metabolismus MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- stres endoplazmatického retikula genetika fyziologie MeSH
- transkriptom genetika MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- messenger RNA MeSH
The aim was to investigate: changes of inflammatory, stress and cardiac response in patients undergoing open heart surgeries up to five days after the procedure; the association between inflammatory, stress and cardiac response and whether changes in a certain marker can predict short-term patient outcome. Ninety patients were divided into three groups, 30 participants each (on-pump,off-pump revascularization and valve replacement group). The following markers were measured:complete blood count, CRP, IL-6, IL-10, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1), cortisol, CK and hsTnT in 5 points. Resistin increased in all three groups. Lower IL-10 levels were found after the surgery and higher levels of leptin and MCP-1 in the off-pump than in the on-pump group. Off-pump group had higher values of IL-6, IL-10, leptin, resistin and MCP-1 and lower levels of CK and hsTnT 24 after surgery than the on-pump group. We found significant correlation between MCP-1 and resistin. The difference between resistin at time points 2 and 3 significantly predicted transfusion needs; while the difference between CRP and resistin before and at the end of the surgery together with the difference between leukocytes at the end and 24 hours after the surgery predicted the use of inotropic agents/vasopressors. Cardiac surgeries cause an increase of inflammatory, stress and cardiac markers. Only resistin correlated with MCP-1 which confirms the link between resistin secreted form infiltrated macrophages and enhanced release of MCP-1.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- koronární bypass metody trendy MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- mladý dospělý MeSH
- nekróza MeSH
- nemoci koronárních tepen krev chirurgie MeSH
- onemocnění aortální chlopně krev chirurgie MeSH
- oxidační stres fyziologie MeSH
- revaskularizace myokardu metody trendy MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- mediátory zánětu MeSH
Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24 ± 7.45 vs. 11.22 ± 1.34%, p = 0.025) with a similar trend observed in non-CAD subjects (29.68 ± 7.61 vs. 10.13 ± 2.01%, p = 0.067). T (CD3+) cells were increased (75.33 ± 2.18 vs. 65.24 ± 4.49%, p = 0.032) and CD3- cells decreased (21.17 ± 2.26 vs. 31.64 ± 4.40%, p = 0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22 ± 2.43 vs. 0.96 ± 0.21%, p = 0.039 for CAD and 12.49 ± 5.83 vs. 1.16 ± 0.19%, p = 0.016 for non-CAD) and reduced natural killer (NK) cells (5.96 ± 1.32 vs. 13.22 ± 2.10%, p = 0.012 for CAD and 5.32 ± 1.97 vs. 13.81 ± 2.72%, p = 0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.
- MeSH
- B-lymfocyty MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen krev imunologie metabolismus MeSH
- perikard imunologie metabolismus MeSH
- podkožní tuk imunologie metabolismus MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- T-lymfocyty imunologie metabolismus MeSH
- tuková tkáň imunologie metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Obesity is a known high-risk factor for the development of vascular diseases and chronic kidney disease (CKD). In this study we aimed to elucidate the impact of adipose tissue on the inflammatory state in CDK patients with obesity. PATIENTS AND METHODS: A cohort of 40 patients with CKD (stages 3-4) with mild proteinuria (2.3-3.5 g/day) were analyzed in a prospective cross-sectional study: single blood samples and visceral and subcutaneous samples of adipose tissue were taken from 20 patients with obesity and 20 without obesity (control group) during elective abdominal surgery (laparoscopic cholecystectomy). Serum concentrations of asymmetric dimethylarginine (ADMA), adiponectin, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, pentosidine and monocyte chemoattractant protein-1 were measured. Messenger RNA expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, adiponectin receptors 1 and 2, and immunocompetent cell marker CD68 was measured in subcutaneous and visceral fat samples using real-time PCR. Adipose tissue was examined immunohistochemically for CD68-positive cells. Other biochemical parameters (insulin, glycated hemoglobin, cholesterol, LDL cholesterol, and triglycerides) were assessed in the two groups of patients at the same time. RESULTS: Serum concentrations of ADMA, C-reactive protein, pentosidine, interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly higher in obese CKD patients than in the control group; adiponectin was lower in the obese group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha, CD68, adiponectin receptor-1, and monocyte chemoattractant protein-1 were significantly increased in the obese patients, whereas expression of adiponectin, interleukin-6, and adiponectin receptor-2 did not significantly differ between the patient groups. In general, mRNA expressions were higher in visceral than in subcutaneous samples (P < 0.01 vs. P < 0.05). Increased infiltration of subcutaneous and visceral adipose tissue by CD68-positive immunocompetent cells was found in the obese CKD group. With respect to lipid metabolism parameters, a small but significant increase in levels was found in the obese patients (P < 0.02). Changes in triglycerides were more marked in this group (P < 0.01) and a similar increase was noted in insulin and HbA1c levels (P < 0.02). CONCLUSION: Increased expression of proinflammatory cytokines and increased infiltration by immunocompetent cells were found in adipose tissue of obese patients with CKD stages 3-4. This upregulated inflammation may contribute to the induction of a systemic proinflammatory state in patients with CKD and could accelerate the progression of renal dysfunction.
- MeSH
- chronická renální insuficience komplikace metabolismus MeSH
- cytokiny metabolismus MeSH
- imunologické faktory metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita komplikace metabolismus MeSH
- tkáňová distribuce MeSH
- tuková tkáň metabolismus MeSH
- zánět komplikace metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- imunologické faktory MeSH